Skip to main content

Part of the book series: Advances in Experimental Medicine and Biology ((AIM,volume 956))

Abstract

DNA methylation is the covalent modification of DNA that affects its function, without altering DNA sequences. Three important roles of DNA methylation include intrauterine programming, acquired predisposition, and transgenerational inheritance. A wide variety of factors can affect DNA methylation. Intrauterine programming involves drastic changes in DNA methylation patterns during cellular development and differentiation, which have a long-lasting effect on the predisposition of offspring. Influences from the mother, including maternal nutritional status, modify intrauterine epigenetic programming. In contrast to the rapid and drastic changes in utero, postnatal factors in daily life can also continue to slowly and dynamically change DNA methylation patterns in both somatic and germ cells. Epigenetic changes occurring in germ cell DNA exert a transgenerational impact on the phenotype of future generations, thus providing a means for ancestral transmission of environmental experiences. Despite adaptive ability, mismatch effect of transgenerational inheritance could be potentially harmful to health if environment has changed, and the acquired acclimatization is no longer beneficial. Increasing evidence from both human and animal studies indicates that DNA methylation exerts a causal impact on the development of hypertension. Therefore, an adverse outcome of maternal malnutrition could be the development of hypertension in offspring, whereby nutritional factors or disease conditions could induce phenotypes susceptible to hypertension through alteration of DNA methylation patterns. These factors are likely to alter DNA methylation patterns in all tissues including germ cells, and despite no direct evidence of an association between transgenerational epigenetic inheritance and hypertension, it is likely to play a role.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Adeyemo A, Gerry N, Chen G, Herbert A, Doumatey A, Huang H et al (2009) A genome-wide association study of hypertension and blood pressure in African Americans. PLoS Genet 5(7):e1000564

    Article  PubMed  PubMed Central  Google Scholar 

  • Alikhani-Koopaei R, Fouladkou F, Frey FJ, Frey BM (2004) Epigenetic regulation of 11 beta-hydroxysteroid dehydrogenase type 2 expression. J Clin Invest 114(8):1146–1157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anway MD, Cupp AS, Uzumcu M, Skinner MK (2005) Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308(5727):1466–1469

    Article  CAS  PubMed  Google Scholar 

  • Arab K, Park YJ, Lindroth AM, Schafer A, Oakes C, Weichenhan D et al (2014) Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A. Mol Cell 55(4):604–614

    Article  CAS  PubMed  Google Scholar 

  • Arai Y, Ohgane J, Yagi S, Ito R, Iwasaki Y, Saito K et al (2011) Epigenetic assessment of environmental chemicals detected in maternal peripheral and cord blood samples. J Reprod Dev 57(4):507–517

    Article  CAS  PubMed  Google Scholar 

  • Beilin LJ (1990) Diet and lifestyle in hypertension: changing perspectives. J Cardiovasc Pharmacol 16(Suppl 7):S62–S66

    Article  PubMed  Google Scholar 

  • Bind MA, Zanobetti A, Gasparrini A, Peters A, Coull B, Baccarelli A et al (2014) Effects of temperature and relative humidity on DNA methylation. Epidemiology 25(4):561–569

    Article  PubMed  PubMed Central  Google Scholar 

  • Bogdarina I, Welham S, King PJ, Burns SP, Clark AJ (2007) Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. Circ Res 100(4):520–526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bogdarina I, Haase A, Langley-Evans S, Clark AJ (2010) Glucocorticoid effects on the programming of AT1b angiotensin receptor gene methylation and expression in the rat. PLoS ONE 5(2):e9237

    Article  PubMed  PubMed Central  Google Scholar 

  • Bohacek J, Mansuy IM (2015) Molecular insights into transgenerational non-genetic inheritance of acquired behaviours. Nat Rev Genet 16(11):641–652

    Article  CAS  PubMed  Google Scholar 

  • Bygren LO, Tinghog P, Carstensen J, Edvinsson S, Kaati G, Pembrey ME et al (2014) Change in paternal grandmothers’ early food supply influenced cardiovascular mortality of the female grandchildren. BMC Genet 15:12

    Article  PubMed  PubMed Central  Google Scholar 

  • Chang H, Zhang T, Zhang Z, Bao R, Fu C, Wang Z et al (2011) Tissue-specific distribution of aberrant DNA methylation associated with maternal low-folate status in human neural tube defects. J Nutr Biochem 22(12):1172–1177

    Article  CAS  PubMed  Google Scholar 

  • Chen CC, Wang KY, Shen CK (2013) DNA 5-methylcytosine demethylation activities of the mammalian DNA methyltransferases. J Biol Chem 288(13):9084–9091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen D, Zhang A, Fang M, Fang R, Ge J, Jiang Y et al (2014) Increased methylation at differentially methylated region of GNAS in infants born to gestational diabetes. BMC Med Genet 15:108

    Article  PubMed  PubMed Central  Google Scholar 

  • Chhabra D, Sharma S, Kho AT, Gaedigk R, Vyhlidal CA, Leeder JS et al (2014) Fetal lung and placental methylation is associated with in utero nicotine exposure. Epigenetics 9(11):1473–1484

    Article  PubMed  PubMed Central  Google Scholar 

  • Cossetti C, Lugini L, Astrologo L, Saggio I, Fais S, Spadafora C (2014) Soma-to-germline transmission of RNA in mice xenografted with human tumour cells: possible transport by exosomes. PLoS ONE 9(7):e101629

    Article  PubMed  PubMed Central  Google Scholar 

  • Demura M, Wang F, Yoneda T, Karashima S, Cheng Y, Yamagishi M et al (2010) Epigenetic transcriptional repression of the human CYP11B2 gene. Endocr J 57:S339

    Article  Google Scholar 

  • Demura M, Demura Y, Takeda Y, Saijoh K (2015) Dynamic regulation of the angiotensinogen gene by DNA methylation, which is influenced by various stimuli experienced in daily life. Hypertens Res 38(8):519–527

    Article  CAS  PubMed  Google Scholar 

  • Denham J, O’Brien BJ, Harvey JT, Charchar FJ (2015) Genome-wide sperm DNA methylation changes after 3 months of exercise training in humans. Epigenomics 7(5):717–731

    Article  CAS  PubMed  Google Scholar 

  • Devanapally S, Ravikumar S, Double-stranded JAM, RNA (2015) made in C. elegans neurons can enter the germline and cause transgenerational gene silencing. Proc Natl Acad Sci U S A 112(7):2133–2138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dewey FE, Grove ME, Pan C, Goldstein BA, Bernstein JA, Chaib H et al (2014) Clinical interpretation and implications of whole-genome sequencing. JAMA 311(10):1035–1045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Di Ruscio A, Ebralidze AK, Benoukraf T, Amabile G, Goff LA, Terragni J et al (2013) DNMT1-interacting RNAs block gene-specific DNA methylation. Nature 503(7476):371–376

    Article  PubMed  PubMed Central  Google Scholar 

  • Dias BG, Ressler KJ (2014) Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci 17(1):89–96

    Article  CAS  PubMed  Google Scholar 

  • Drake AJ, O’Shaughnessy PJ, Bhattacharya S, Monteiro A, Kerrigan D, Goetz S et al (2015) In utero exposure to cigarette chemicals induces sex-specific disruption of one-carbon metabolism and DNA methylation in the human fetal liver. BMC Med 13:18

    Article  PubMed  PubMed Central  Google Scholar 

  • Feldmann A, Ivanek R, Murr R, Gaidatzis D, Burger L, Schubeler D (2013) Transcription factor occupancy can mediate active turnover of DNA methylation at regulatory regions. PLoS Genet 9(12):e1003994

    Article  PubMed  PubMed Central  Google Scholar 

  • Franceschini N, Fox E, Zhang Z, Edwards TL, Nalls MA, Sung YJ et al (2013) Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations. Am J Hum Genet 93(3):545–554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Franklin TB, Russig H, Weiss IC, Graff J, Linder N, Michalon A et al (2010) Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry 68(5):408–415

    Article  PubMed  Google Scholar 

  • Friso S, Pizzolo F, Choi SW, Guarini P, Castagna A, Ravagnani V et al (2008) Epigenetic control of 11 beta-hydroxysteroid dehydrogenase 2 gene promoter is related to human hypertension. Atherosclerosis 199(2):323–327

    Article  CAS  PubMed  Google Scholar 

  • Ganesh SK, Tragante V, Guo W, Guo Y, Lanktree MB, Smith EN et al (2013) Loci influencing blood pressure identified using a cardiovascular gene-centric array. Hum Mol Genet 22(8):1663–1678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Govorko D, Bekdash RA, Zhang C, Sarkar DK (2012) Male germline transmits fetal alcohol adverse effect on hypothalamic proopiomelanocortin gene across generations. Biol Psychiatry 72(5):378–388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo H, Zhu P, Yan L, Li R, Hu B, Lian Y et al (2014) The DNA methylation landscape of human early embryos. Nature 511(7511):606–610

    Article  CAS  PubMed  Google Scholar 

  • Guo F, Yan L, Guo H, Li L, Hu B, Zhao Y et al (2015) The transcriptome and DNA methylome landscapes of human primordial germ cells. Cell 161(6):1437–1452

    Article  CAS  PubMed  Google Scholar 

  • Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES et al (2008) Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A 105(44):17046–17049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hong KW, Go MJ, Jin HS, Lim JE, Lee JY, Han BG et al (2010) Genetic variations in ATP2B1, CSK, ARSG and CSMD1 loci are related to blood pressure and/or hypertension in two Korean cohorts. J Hum Hypertens 24(6):367–372

    Article  CAS  PubMed  Google Scholar 

  • International Consortium for Blood Pressure Genome-Wide Association, Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD et al (2011) Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478(7367):103–109

    Article  Google Scholar 

  • Ishikawa K, Tsunekawa S, Ikeniwa M, Izumoto T, Iida A, Ogata H et al (2015) Long-term pancreatic beta cell exposure to high levels of glucose but not palmitate induces DNA methylation within the insulin gene promoter and represses transcriptional activity. PLoS ONE 10(2):e0115350

    Article  PubMed  PubMed Central  Google Scholar 

  • James SJ, Pogribny IP, Pogribna M, Miller BJ, Jernigan S, Melnyk S (2003) Mechanisms of DNA damage, DNA hypomethylation, and tumor progression in the folate/methyl-deficient rat model of hepatocarcinogenesis. J Nutr 133(11 Suppl 1):3740S–3747S

    CAS  PubMed  Google Scholar 

  • Kaati G, Bygren LO, Edvinsson S (2002) Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Genet 10(11):682–688

    Article  CAS  PubMed  Google Scholar 

  • Kangaspeska S, Stride B, Metivier R, Polycarpou-Schwarz M, Ibberson D, Carmouche RP et al (2008) Transient cyclical methylation of promoter DNA. Nature 452(7183):112–115

    Article  CAS  PubMed  Google Scholar 

  • Kato N, Takeuchi F, Tabara Y, Kelly TN, Go MJ, Sim X et al (2011) Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. Nat Genet 43(6):531–538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kato N, Loh M, Takeuchi F, Verweij N, Wang X, Zhang W et al (2015) Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation. Nat Genet

    Google Scholar 

  • Kwong WY, Wild AE, Roberts P, Willis AC, Fleming TP (2000) Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development 127(19):4195–4202

    CAS  PubMed  Google Scholar 

  • Lee HA, Baek I, Seok YM, Yang E, Cho HM, Lee DY et al (2010) Promoter hypomethylation upregulates Na+-K+-2Cl- cotransporter 1 in spontaneously hypertensive rats. Biochem Biophys Res Commun 396(2):252–257

    Article  CAS  PubMed  Google Scholar 

  • Lee HJ, Hore TA, Reik W (2014) Reprogramming the methylome: erasing memory and creating diversity. Cell Stem Cell 14(6):710–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A et al (2009) Genome-wide association study of blood pressure and hypertension. Nat Genet 41(6):677–687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Hui AM, Sun L, Hasegawa K, Torzilli G, Minagawa M et al (2004) p16INK4A hypermethylation is associated with hepatitis virus infection, age, and gender in hepatocellular carcinoma. Clin Cancer Res 10(22):7484–7489

    Article  CAS  PubMed  Google Scholar 

  • Lienert F, Wirbelauer C, Som I, Dean A, Mohn F, Schubeler D (2011) Identification of genetic elements that autonomously determine DNA methylation states. Nat Genet 43(11):1091–1097

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Liu P, Yang C, Cowley AW Jr, Liang M (2014) Base-resolution maps of 5-methylcytosine and 5-hydroxymethylcytosine in Dahl S rats: effect of salt and genomic sequence. Hypertension 63(4):827–838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu F, Sun Q, Wang L, Nie S, Li J (2015) Bioinformatics analysis of abnormal DNA methylation in muscle samples from monozygotic twins discordant for type 2 diabetes. Mol Med Rep 12(1):351–356

    CAS  PubMed  Google Scholar 

  • MacArthur DG, Tyler-Smith C (2010) Loss-of-function variants in the genomes of healthy humans. Hum Mol Genet 19(R2):R125–R130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • MacArthur DG, Balasubramanian S, Frankish A, Huang N, Morris J, Walter K et al (2012) A systematic survey of loss-of-function variants in human protein-coding genes. Science 335(6070):823–828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maekita T, Nakazawa K, Mihara M, Nakajima T, Yanaoka K, Iguchi M et al (2006) High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res 12(3 Pt 1):989–995

    Article  CAS  PubMed  Google Scholar 

  • Marchal C, Miotto B (2015) Emerging concept in DNA methylation: role of transcription factors in shaping DNA methylation patterns. J Cell Physiol 230(4):743–751

    Article  CAS  PubMed  Google Scholar 

  • Metivier R, Gallais R, Tiffoche C, Le Peron C, Jurkowska RZ, Carmouche RP et al (2008) Cyclical DNA methylation of a transcriptionally active promoter. Nature 452(7183):45–50

    Article  CAS  PubMed  Google Scholar 

  • Miller CA, Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53(6):857–869

    Article  CAS  PubMed  Google Scholar 

  • Miller CA, Gavin CF, White JA, Parrish RR, Honasoge A, Yancey CR et al (2010) Cortical DNA methylation maintains remote memory. Nat Neurosci 13(6):664–666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakajima T, Yamashita S, Maekita T, Niwa T, Nakazawa K, Ushijima T (2009) The presence of a methylation fingerprint of Helicobacter pylori infection in human gastric mucosae. Int J Cancer 124(4):905–910

    Article  CAS  PubMed  Google Scholar 

  • Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L et al (2009) Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet 41(6):666–676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nilsson E, Matte A, Perfilyev A, de Mello VD, Kakela P, Pihlajamaki J et al (2015) Epigenetic alterations in human liver from subjects with type 2 diabetes in parallel with reduced folate levels. J Clin Endocrinol Metab 100(11):E1491–E1501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oka D, Yamashita S, Tomioka T, Nakanishi Y, Kato H, Kaminishi M et al (2009) The presence of aberrant DNA methylation in noncancerous esophageal mucosae in association with smoking history: a target for risk diagnosis and prevention of esophageal cancers. Cancer 115(15):3412–3426

    Article  CAS  PubMed  Google Scholar 

  • Okae H, Chiba H, Hiura H, Hamada H, Sato A, Utsunomiya T et al (2014) Genome-wide analysis of DNA methylation dynamics during early human development. PLoS Genet 10(12):e1004868

    Article  PubMed  PubMed Central  Google Scholar 

  • Oliver WJ, Cohen EL, Neel JV (1975) Blood pressure, sodium intake, and sodium related hormones in the Yanomamo Indians, a “no-salt” culture. Circulation 52(1):146–151

    Article  CAS  PubMed  Google Scholar 

  • Padmanabhan S, Melander O, Johnson T, Di Blasio AM, Lee WK, Gentilini D et al (2010) Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension. PLoS Genet 6(10):e1001177

    Article  PubMed  PubMed Central  Google Scholar 

  • Pembrey ME, Bygren LO, Kaati G, Edvinsson S, Northstone K, Sjostrom M et al (2006) Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet 14(2):159–166

    Article  PubMed  Google Scholar 

  • Pizzolo F, Friso S, Morandini F, Antoniazzi F, Zaltron C, Udali S et al (2015) Apparent mineralocorticoid excess by a novel mutation and epigenetic modulation by HSD11B2 promoter methylation. J Clin Endocrinol Metab 100(9):E1234–E1241

    Article  PubMed  Google Scholar 

  • Riviere G, Lienhard D, Andrieu T, Vieau D, Frey BM, Frey FJ (2011) Epigenetic regulation of somatic angiotensin-converting enzyme by DNA methylation and histone acetylation. Epigenetics 6(4):478–489

    Article  CAS  PubMed  Google Scholar 

  • Ronn T, Volkov P, Davegardh C, Dayeh T, Hall E, Olsson AH et al (2013) A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet 9(6):e1003572

    Article  PubMed  PubMed Central  Google Scholar 

  • Ronn T, Volkov P, Gillberg L, Kokosar M, Perfilyev A, Jacobsen AL et al (2015) Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood. Hum Mol Genet 24(13):3792–3813

    PubMed  Google Scholar 

  • Roseboom TJ, van der Meulen JH, Ravelli AC, van Montfrans GA, Osmond C, Barker DJ et al (1999) Blood pressure in adults after prenatal exposure to famine. J Hypertens 17(3):325–330

    Article  CAS  PubMed  Google Scholar 

  • Roseboom TJ, van der Meulen JH, Ravelli AC, Osmond C, Barker DJ, Bleker OP (2001a) Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Mol Cell Endocrinol 185(1-2):93–98

    Article  CAS  PubMed  Google Scholar 

  • Roseboom TJ, van der Meulen JH, Ravelli AC, Osmond C, Barker DJ, Bleker OP (2001b) Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Twin Res 4(5):293–298

    Article  CAS  PubMed  Google Scholar 

  • Serra RW, Fang M, Park SM, Hutchinson L, Green MR (2014) A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype. Elife 3:e02313

    Article  PubMed  PubMed Central  Google Scholar 

  • Slieker RC, Roost MS, van Iperen L, Suchiman HE, Tobi EW, Carlotti F et al (2015) DNA methylation landscapes of human fetal development. PLoS Genet 11(10):e1005583

    Article  PubMed  PubMed Central  Google Scholar 

  • Smolarek I, Wyszko E, Barciszewska AM, Nowak S, Gawronska I, Jablecka A et al (2010) Global DNA methylation changes in blood of patients with essential hypertension. Med Sci Monit 16(3):CR149–CR155

    CAS  PubMed  Google Scholar 

  • Szyf M (2015) Nongenetic inheritance and transgenerational epigenetics. Trends Mol Med 21(2):134–144

    Article  PubMed  Google Scholar 

  • Takeshima H, Yamashita S, Shimazu T, Niwa T, Ushijima T (2009) The presence of RNA polymerase II, active or stalled, predicts epigenetic fate of promoter CpG islands. Genome Res 19(11):1974–1982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang WW, Dietmann S, Irie N, Leitch HG, Floros VI, Bradshaw CR et al (2015) A unique gene regulatory network resets the human germline epigenome for development. Cell 161(6):1453–1467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang A, Huang Y, Li Z, Wan S, Mou L, Yin G et al (2016) Analysis of a four generation family reveals the widespread sequence-dependent maintenance of allelic DNA methylation in somatic and germ cells. Sci Rep 6:19260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thillainadesan G, Chitilian JM, Isovic M, Ablack JN, Mymryk JS, Tini M et al (2012) TGF-beta-dependent active demethylation and expression of the p15ink4b tumor suppressor are impaired by the ZNF217/CoREST complex. Mol Cell 46(5):636–649

    Article  CAS  PubMed  Google Scholar 

  • Thomassin H, Flavin M, Espinas ML, Grange T (2001) Glucocorticoid-induced DNA demethylation and gene memory during development. EMBO J 20(8):1974–1983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tobi EW, Goeman JJ, Monajemi R, Gu H, Putter H, Zhang Y et al (2014) DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat Commun 5:5592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Veenendaal MV, Painter RC, de Rooij SR, Bossuyt PM, van der Post JA, Gluckman PD et al (2013) Transgenerational effects of prenatal exposure to the 1944-45 Dutch famine. BJOG 120(5):548–553

    Article  CAS  PubMed  Google Scholar 

  • Wain LV, Verwoert GC, O’Reilly PF, Shi G, Johnson T, Johnson AD et al (2011) Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. Nat Genet 43(10):1005–1011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wajapeyee N, Malonia SK, Palakurthy RK, Green MR (2013) Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors. Genes Dev 27(20):2221–2226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Falkner B, Zhu H, Shi H, Su S, Xu X et al (2013) A genome-wide methylation study on essential hypertension in young African American males. PLoS ONE 8(1):e53938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang F, Demura M, Cheng Y, Zhu A, Karashima S, Yoneda T et al (2014a) Dynamic CCAAT/enhancer binding protein-associated changes of DNA methylation in the angiotensinogen gene. Hypertension 63(2):281–288

    Article  CAS  PubMed  Google Scholar 

  • Wang KY, Chen CC, Shen CK (2014b) Active DNA demethylation of the vertebrate genomes by DNA methyltransferases: deaminase, dehydroxymethylase or demethylase? Epigenomics 6(3):353–363

    Article  CAS  PubMed  Google Scholar 

  • Watkins AJ, Ursell E, Panton R, Papenbrock T, Hollis L, Cunningham C et al (2008) Adaptive responses by mouse early embryos to maternal diet protect fetal growth but predispose to adult onset disease. Biol Reprod 78(2):299–306

    Article  CAS  PubMed  Google Scholar 

  • Whorwood CB, Firth KM, Budge H, Symonds ME (2001) Maternal undernutrition during early to midgestation programs tissue-specific alterations in the expression of the glucocorticoid receptor, 11beta-hydroxysteroid dehydrogenase isoforms, and type 1 angiotensin ii receptor in neonatal sheep. Endocrinology 142(7):2854–2864

    Article  CAS  Google Scholar 

  • Zhang LN, Liu PP, Wang L, Yuan F, Xu L, Xin Y et al (2013) Lower ADD1 gene promoter DNA methylation increases the risk of essential hypertension. PLoS ONE 8(5):e63455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Yang R, Burwinkel B, Breitling LP, Brenner H (2014) F2RL3 methylation as a biomarker of current and lifetime smoking exposures. Environ Health Perspect 122(2):131–137

    PubMed  Google Scholar 

Download references

Acknowledgements

This chapter was supported by the Japan Society for Takeda Science Foundation (to M Demura).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Masashi Demura .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing AG

About this chapter

Cite this chapter

Demura, M., Saijoh, K. (2016). The Role of DNA Methylation in Hypertension. In: Islam, M.S. (eds) Hypertension: from basic research to clinical practice. Advances in Experimental Medicine and Biology(), vol 956. Springer, Cham. https://doi.org/10.1007/5584_2016_80

Download citation

  • DOI: https://doi.org/10.1007/5584_2016_80

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-44250-1

  • Online ISBN: 978-3-319-44251-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics